When we’re suffering from a bacterial infection, a trip to the doctors to be prescribed antibiotics is commonplace. However, there are a wide range of antibiotics available, and they vary both in their usage and their mechanism of action. This graphic summarises the major classes, and also gives a brief insight into the manner in which they combat bacterial infections; we’ll also consider each of the groups in turn, as well as bacterial resistance to each.
Bacteria themselves can be divided into two broad classes – Gram-positive and Gram-negative. The classes derive these names from the Gram test, which involves the addition of a violet dye to the bacteria. Gram-positive bacteria retain the colour of the dye, whilst Gram-negative bacteria do not, and are instead coloured red or pink. Gram-negative bacteria are more resistant to antibodies and antibiotics than Gram-positive bacteria, because they have a largely impermeable cell wall. The bacteria responsible for MRSA and acne are examples of Gram-positive bacteria, whilst those responsible for Lyme disease and pneumonia are examples of Gram-negative bacteria.
Beta-lactams are a wide range of antibiotics, the first of which to be discovered was penicillin, which Alexander Fleming identified in 1928. All beta-lactam antibiotics contain a beta-lactam ring; they include penicillins, such as amoxicillin, and cephalosporins. They work by interfering with the synthesis of peptidoglycan, an important component of the bacterial cell wall, and are mostly used against gram-positive bacteria. Bacteria can, however, develop resistance to beta-lactams via several routes, including the production of enzymes that break down the beta-lactam ring. In the NHS, penicillins are the most commonly prescribed antibiotics, with amoxicillin being the most common in the class.
Prontosil, a sulfonamide, was the first commercially available antibiotic, developed in 1932. A significant number of sulfonamide antibiotics were subsequently developed, defined as broad-spectrum antibiotics capable of acting on both Gram-positive and Gram-negative bacteria. Unlike the beta-lactams, they do not act by directly killing the bacteria, but by inhibiting bacterial synthesis of the B vitamin folate, thus preventing growth and reproduction of the bacteria. In the present day, sulfonamides are rarely used, partially due to the development of bacterial resistance, but also due to concern about unwanted effects such as hepatotoxicity.
Aminoglycosides inhibit the synthesis of proteins in bacteria, eventually leading to cell death. They are only effective against certain Gram-negative bacteria, as well as some Gram-positive bacteria, but are not absorbed during digestion, so must be injected. In the treatment of tuberculosis, streptomycin was the first drug found to be effective; however, due to issues with toxicity of aminoglycosides, their present day use is limited.
Tetracyclines are broad-spectrum antibiotics, active against both Gram-positive and Gram-negative bacteria. Like the sulfonamides, they inhibit protein synthesis, inhibiting growth and reproduction of bacteria. Their use is decreasing to increasing instances of bacterial resistance; however, they still find use in treatment of acne, urinary tract, and respiratory tract infections, as well as chlamydia infections. They must be taken in isolation, often two hours before or after eating, as they can easily bind with food, reducing their absorption.
Another broad-spectrum antibiotic, chloramphenicol also acts by inhibiting protein synthesis, and thus growth and reproduction of bacteria. However, it is also bactericidal against a limited number of bacteria. Due to the possibility of serious toxic effects, in developed countries it is generally only used in cases where infections are deemed to be life-threatening, although it is also occasionally used in the treatment of eye infections. Despite this, it is a much more common antibiotic in developing countries due to its low cost and availability, and is recommended by the World Health Organisation as an effective first line treatment for meningitis in those countries with a low income.
Much like the beta-lactams, the macrolides are mainly effective against Gram-positive bacteria; however, they act in a bacteriostatic manner, preventing growth and reproduction by inhibiting protein synthesis. Their effectiveness is marginally broader than that of penicillins, and they have been shown to be effective against several species of bacteria that penicillins are not. Whilst some bacterial species have developed resistance to macrolides, they are still the second most commonly prescribed antibiotics in the NHS, with erythromycin being the most commonly prescribed in the class.
Glycopeptides include the drug vancomycin – commonly used as a ‘drug of last resort’, when other antibiotics have failed. Whilst this used to be the last line of defence against infections, particularly MRSA, the more recent development of newer antibiotics in other classes has provided other options. Nonetheless, there remain strict guidelines on the circumstances in which vancomycin can be used to treat infections, in order to delay the development of resistance. The bacteria against which glycopeptides are active are otherwise somewhat limited, and in most they inhibit growth and reproduction rather than killing bacteria directly.
Oxazolidinones are active against Gram-positive bacteria, and act by inhibiting protein synthesis, and hence growth and reproduction. Linezolid, approved for use in 2000, was the first marketed antibiotic in the class, although the compound cycloserine has been used as a second line tuberculosis treatment since 1956. Whilst linezolid is expensive, resistance seems to be developing relatively slowly since its introduction.
This class of antibiotics are effective against Gram-positive bacteria, as well as some Gram-negative bacteria. They inhibit the production of RNA, which has important biological roles inside the cells of the bacteria, and as such leads to the death of the bacterial cells. A subclass of antibiotics, rifamycins, are used to treat tuberculosis and leprosy. Uncommonly, ansamycins can also demonstrate anti-viral activity.
Quinolones are bactericidal compounds that interfere with the replication and transcription of DNA in bacteria cells. They are broad-spectrum antibiotics, and are widely used for urinary tract infections, as well as other hospital-acquired infections where resistance to older classes of antibiotics is suspected. Additionally, their use for veterinary purposes is widespread; a use that has been criticised in some quarters for hastening the development of resistance. Resistance to quinolones can be particularly rapid in its development; in the US, they were the most commonly prescribed antibiotics in 2002, and their prescription for unrecommended conditions or viral infections is also thought to be a significant contributor to the development of resistance.
Streptogramins are unusual in that they are usually administered as a combination of two antibiotic drugs from the different groups within the class: streptogramin A and streptogramin B. On their own, these compounds only show growth-inhibiting activity, but combined they have a synergistic effect and are capable of directly killing bacteria cells, by inhibiting the synthesis of proteins. They are often used to treat resistant infections, although resistance to the streptogramins themselves has also developed.
Discovered in 1987, lipopeptides are the most recent class of antibiotics, and are bactericidal against Gram-positive bacteria. Daptomycin is the most commonly used member of the class; it has a unique mechanism of action, disrupting several aspects of cell membrane function in bacteria. This unique mechanism of action also seems to be advantageous in that, currently, incidences of resistance to the drug seem to be rare – though they have been reported. It is given via injection, and commonly used to treat infections in the skin and tissue.
Bacterial resistance to antibiotics is on the rise, to the extent that it has been made the focus of this year’s Longitude Prize. The prize is offering a £10 million prize fund for the development of a cheap and easy to use bacterial infection test kit, in the hope that this will allow doctors to prescribe the correct antibiotics at the correct time for patients, and also prevent the prescribing of antibiotics in the cases of viral infections. It’s hoped both of these measures will help slow the development of antibiotic resistance in bacteria.
References & Further Reading
- Types of antibiotics – Biotopics.co.uk
- Novel Classes of Antibiotics – A R M Coates & others
- Antibiotics – recover the lost art of drug discovery – K Lewis
- Antibacterial drugs & medications – EMedical Guild